Some of his earliest work is for DC Comics's House of Secrets and a run on Swamp Thing (Vol. 1, #14-18, 21 and 22), following Len Wein and preceding Gerry Conway, illustrated by Nestor Redondo. Michelinie also did a run on Aquaman in Adventure Comics which led to the revival of the Sea King's own title in 1977. In the last story of the Adventure Comics, #452, Black Manta killed Arthur Curry Jr. by suffocation. The infant's death has affected the character ever since.

His most famous works include two noted runs on the Iron Man series, with co-writer (and inker) Bob Layton, in the late 1970s and early 1980s which introduced the character's serious problem with alcoholism, his specialized power armor variants and his new enmities with Justin Hammer and Victor Von Doom. He also introduced one of Stark's closest comrades, the fearless pilot, Jim Rhodes. His most noted cliffhanger was when Tony Stark was thrown out of S.H.I.E.L.D.'s helicarrier and had to don his armor completely to use its flight function before he hit the ground.

From the late 1980s to early '90s, he also wrote a popular run on The Amazing Spider-Man series which featured the art of Todd McFarlane, Erik Larsen, Mark Bagley and introduced the popular supervillain Venom. Michelinie had planned to introduce Venom earlier and did include a "teaser" scene in Web of Spider-Man #18, in which Peter Parker is pushed by an offscreen Venom into the path of an oncoming train, the symbiote being immune to Spider-Man's "spider sense" that would have normally warned him of the attack. This was the first of what was to be several clues leading to the reveal of Venom. Michelinie left Web of Spider-Man shortly after and was not able to continue the introduction of Venom until his time of writing on The Amazing Spider-Man, which started with issue #290. Subsequently he became the writer of Action Comics following Roger Stern's lengthy run, which ended with #700. He also worked at Valiant Comics on the books Rai, H.A.R.D. Corps and Turok: Dinosaur Hunter.

He also has the record of having the second longest run as writer (from 1987—1994) on The Amazing Spider-Man comic (behind only Stan Lee). Michelinie's last issue was issue #388 (April 1994).

Michelinie returned to creating comics by teaming-up with Bob Layton and Dick Giordano to form Future Comics. The company closed down after only two and a half years in business in 2004.

In 2008, he re-teamed with Layton once again for a four-issue Iron Man: Legacy of Doom miniseries and Iron Man: The End #1 one-shot for Marvel Comics.

In the credits of numerous comics, his name is misspelled as "David Micheline".